Differences in phospholipid metabolism that appear to exist between cancer cells and the normal cells of their apparent origin might be exploited in the design of agents effective against some types of cancer. Such agents, being directed toward phospholipid pathways, would introduce classes of chemotherapeutic agents that function by mechanisms different from those agents presently in clinical use. Agents functioning by novel mechanisms hopefully would not necessarily share the common limitations of nucleic acid anti-metabolites and alkylating agents such as toxicity for dividing normal cells and suppression of immune mechanisms. The absence of NAD-linked glycerol-3-P dehydrogenase in many types of cancer cells, and the possible greater reliance of such cells on pathways to the de novo synthesis of phospholipids through acylation and subsequent reduction of dihydroxyacetone-P suggests a possible chemotherapeutic approach. L-1-Fluorodeoxy-(L-1-FdG3P) D-1-fluorodeoxy- glycerol-3-P (D-1-FdG3P), or 1-fluorodeoxy-hydroxyacetone-3-P (FHAP) or L-1-FdG3P might differentially affect cells unable to interconvert FHAP and L-1-FdG3P. Such differential effects might occur directly by virtue of selective metabolism of FHAP or L-1-FdG3P to toxic products, or indirectly by inhibition of enzymes in phospholipid or triose metabolism by FHAP, or D- or L-1FdG3P. Access to cells might be gained by use of precursors able to generate FHAP intra-cellularly: agents such as 3-fluorodeoxy-1-fructose, 3-fluorodeoxy-D-mannose, 3-fluorodeoxy-D-sorbitol or 1-fluoro-3-hydroxy acetone. The fluorohexoses might also exert differential effects on normal and neoplastic cells by virtue of differences in fructose metabolism that are known to exist between some normal and neoplastic cells, and by virtue of differences in hexose transport that may exist between them. In order to extend this chemotherapeutic approach more rationally toward differences in phospholipid synthesis that may exist between normal and neoplastic cells, structural studies on NAD-linked glycerol-3-P dehydrogenases geared toward elucidation of its metabolic role in different tissues including brain, mammary gland, and leucocytes constitute an important aspect of the project.